Rheumatoid arthritis (RA) is a systemic autoimmune disease with high incidence rate and long course. The patients suffer from distress and even lose the ability for work and life. It is difficult to be cured and easy to relapse.
So far there are no satisfactory drugs to therapy rheumatoid arthritis. In the present available drugs for therapy of this disease include steroid anti-inflammatory drugs (SAIDs) and non-steroid anti-inflammatory drugs (NSAIDs). Although many drugs were supplied, all of them have serious side-effects. For example, SAIDs can make the body produce hormone-dependence, influence the metabolism and inhibit the immune system. Since NSAIDs inhibit cyclooxygenase and reduce production of prostaglands, they can damage the gastrointestinal mucosa.
The pathological process of rheumatoid arthritis involves many inflammatory mediators. Platelet activating factor (PAF) is the important ones which belongs to phospholipids and is produced by several inflammatory cells. It can induce various responses after binding to its receptor and coupling through G-protein. PAF receptor antagonists compete with PAF for their receptors, so they can effectively inhibit inflammation. The previous investigation also shows PAF can enhance the production of other inflammatory mediators, the expression of cytokines, activate nuclear factor and influence many pathological process related to inflammation. PAF receptor has became an important target for developing new anti-inflammatory and immuno-regulatory drugs. Moreover, PAF receptor antagonists can protect the gastrointestinal mucosa which is the protrusive advantage comparing with the launched anti-inflammatory drugs.
In the recent years some natural and synthesized compounds which have PAF receptor antagonistic effect were found. More than 60 pharmaceutical companies and institutes study on this field. About 550 compounds were synthesized and examined in biological experiments. Among them 18 enter the phase I clinic trail , 17 enter the phase II clinic trail, 2(BN52021 and Y-24180) enter the phase III clinic trail. Especially, rheumatoid arthritis is one of the indications for those compounds. Among them, 2 compounds are researched at the stage of biological examination. Those compounds, such as CV-6209 can inhibit rat paw swelling induced by several inflamed agents (for instance PAF, carrageenan, histamine, 5-serotonin). BN50730 significantly improves the symptom of patients with rheumatoid arthritis after administration for 4 weeks. WEB2170 can inhibit the increase of new vessels in mouse angiogenesis model induced by synovial fluid of patient with rheumatoid arthritis. WEB2170 can inhibit the increase of TNF-αlevel in synovial fluid of rat ankle joint induced by immune complex. A-85783 can significantly inhibit the rat ear edema induced by PAF or PMA. BN50730 can significantly inhibit the joint swelling of mouse with arthritis induced by type III collagen, decrease the precipitation of fibronectin and the consumption of proteoglycan in cartilage. BN50730 can reduce the early activity of NF-κB and the expression of TNF-αmRNA in the infected mice. LDP-392 can significantly inhibit the mouse ear edema induced by arachidonic acid.